Wound healing is a dynamic process that involves many cellular and chemical elements, and results in the rapid sealing of the wound, followed by a longer-term tissue remodeling process in which the wound is healed. Wounds can be caused, without limitation, by mechanical injury, thermal injury, radiation injury or infection. Wounds may occur as a typical part of a surgical or other medical procedure. In many instances, scar formation is a natural result of the wound-healing process due to a fibrotic response. In many instances, scarring as a result of the fibrotic response in wound healing is benign. In other instances, scarring can be undesirable, if not harmful, resulting in scar tissue that is at a minimum, aesthetically displeasing, and at worse, harmful to the function of an organ or biological system in a subject, such as the heart or eye. In most human tissues, a pathological consequence of an inappropriate or poorly regulated tissue repair process is described as fibrosis.
One example of a pathological fibrotic response is the fibrotic response that can occur with corneal injury. In the United States, over 2.4 million people annually experience traumatic eye injuries. Not only are these injuries exquisitely painful when the cornea is involved, but the consequence of improper healing can be debilitating. Also of note, in 2005, an estimated 928,737 Americans underwent refractive surgery. The most common techniques used were LASIK (laser in situ keratomeliusis) or PRK (photorefractive keratectomy). Indeed refractive surgeries are the most common eye surgeries next to cataract extraction. However, manipulation of the cornea involved in these procedures is not without complications, among them being corneal haze, severely dry eyes, undesirable refractive outcomes, and keratitis—all of which could be attenuated by ideal corneal wound healing. An injury to corneal stroma results in activation of corneal keratocytes to proliferative fibroblasts or contractile myofibroblasts, which are often responsible for the development of contractile, nontransparent scar tissue. This outcome is highly undesirable following an injury or refractive surgery. Currently drugs or chemicals, such as mitomycin-C, which are used to prevent cellular activation, proliferation and fibrotic response following corneal or glaucoma filtration surgeries are harsh and can cause irreversible damage to the normal tissue. A less-toxic option for management, for example prevention and/or treatment, of the fibrotic response to corneal injury is desirable. More generally, treatment for the management of the fibrotic response in any tissue is desirable.